ID   GUC2F_MOUSE             Reviewed;        1108 AA.
AC   Q5SDA5; Q8BLL8;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Retinal guanylyl cyclase 2 {ECO:0000303|PubMed:17255100};
DE            EC=4.6.1.2 {ECO:0000250|UniProtKB:O02740};
DE   AltName: Full=Guanylate cyclase 2F;
DE   Flags: Precursor;
GN   Name=Gucy2f {ECO:0000312|MGI:MGI:105119};
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 [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Retina;
RX   PubMed=15718098; DOI=10.1016/j.ygeno.2004.11.001;
RA   Shearstone J.R., Wang Y.E., Clement A., Allaire N.E., Yang C., Worley D.S.,
RA   Carulli J.P., Perrin S.;
RT   "Application of functional genomic technologies in a mouse model of retinal
RT   degeneration.";
RL   Genomics 85:309-321(2005).
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 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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-846.
RC   STRAIN=C57BL/6J; TISSUE=Retina;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
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   [6]
RP   SUBCELLULAR LOCATION, INTERACTION WITH RD3, AND TISSUE SPECIFICITY.
RX   PubMed=21078983; DOI=10.1073/pnas.1010460107;
RA   Azadi S., Molday L.L., Molday R.S.;
RT   "RD3, the protein associated with Leber congenital amaurosis type 12, is
RT   required for guanylate cyclase trafficking in photoreceptor cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:21158-21163(2010).
CC   -!- FUNCTION: Responsible for the synthesis of cyclic GMP (cGMP) in rods
CC       and cones of photoreceptors (By similarity). Plays an essential role in
CC       phototransduction, by mediating cGMP replenishment. May also
CC       participate in the trafficking of membrane-asociated proteins to the
CC       photoreceptor outer segment membrane (PubMed:17255100).
CC       {ECO:0000250|UniProtKB:O02740, ECO:0000269|PubMed:17255100}.
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:O02740};
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 (By similarity). Interacts with RD3; promotes the
CC       exit of GUCY2F from the endoplasmic reticulum and its trafficking to
CC       the photoreceptor outer segments (PubMed:21078983).
CC       {ECO:0000250|UniProtKB:P51842, ECO:0000269|PubMed:21078983}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P51842}; Single-
CC       pass type I membrane protein {ECO:0000255}. Photoreceptor outer segment
CC       membrane {ECO:0000269|PubMed:21078983}; Single-pass type I membrane
CC       protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Retina. {ECO:0000269|PubMed:21078983}.
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. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Deficient mice exhibit normal retinal morphology.
CC       Electroretinography shows slower recovery of rod from intense
CC       illumination. GUCY2F and GUCY2E double knockout mice does not show any
CC       photoresponse at 4 weeks of age, rods and cones degenerate at about 2
CC       month of age and the intracellular transport of some phototransduction
CC       proteins is impaired. {ECO:0000269|PubMed:17255100}.
CC   -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC       family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR   EMBL; AY651761; AAV54098.1; -; mRNA.
DR   EMBL; AL671916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX324191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC115714; AAI15715.1; -; mRNA.
DR   EMBL; AK044234; BAC31833.1; -; mRNA.
DR   CCDS; CCDS30446.1; -.
DR   RefSeq; NP_001007577.1; NM_001007576.2.
DR   RefSeq; XP_006528904.1; XM_006528841.3.
DR   AlphaFoldDB; Q5SDA5; -.
DR   SMR; Q5SDA5; -.
DR   IntAct; Q5SDA5; 1.
DR   STRING; 10090.ENSMUSP00000044521; -.
DR   iPTMnet; Q5SDA5; -.
DR   PhosphoSitePlus; Q5SDA5; -.
DR   MaxQB; Q5SDA5; -.
DR   PaxDb; 10090-ENSMUSP00000044521; -.
DR   ProteomicsDB; 271368; -.
DR   Antibodypedia; 29460; 117 antibodies from 18 providers.
DR   DNASU; 245650; -.
DR   Ensembl; ENSMUST00000042530.4; ENSMUSP00000044521.4; ENSMUSG00000042282.5.
DR   GeneID; 245650; -.
DR   KEGG; mmu:245650; -.
DR   UCSC; uc009ulq.2; mouse.
DR   AGR; MGI:105119; -.
DR   CTD; 2986; -.
DR   MGI; MGI:105119; Gucy2f.
DR   VEuPathDB; HostDB:ENSMUSG00000042282; -.
DR   eggNOG; KOG1023; Eukaryota.
DR   GeneTree; ENSGT00940000162146; -.
DR   HOGENOM; CLU_001072_1_0_1; -.
DR   InParanoid; Q5SDA5; -.
DR   OMA; QDSQSMR; -.
DR   OrthoDB; 3683909at2759; -.
DR   PhylomeDB; Q5SDA5; -.
DR   TreeFam; TF106338; -.
DR   Reactome; R-MMU-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   BioGRID-ORCS; 245650; 2 hits in 79 CRISPR screens.
DR   PRO; PR:Q5SDA5; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; Q5SDA5; Protein.
DR   Bgee; ENSMUSG00000042282; Expressed in layer of retina and 10 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0120200; C:rod photoreceptor outer segment; IDA: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; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR   GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR   GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:CACAO.
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; 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; 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.
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_0000280445"
FT   TOPO_DOM        51..469
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        470..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;  124425 MW;  8A1456FCB384FA90 CRC64;
     MFLGPWPFSR LLSWFAISSR LSGQHGLPSS KFLRCLCLLA LLPLLRWGQA LPYKIGVIGP
     WTCDPFFSKA LPEVAAALAI ERISRDKTFD RSYSFEYVIL NEDCQTSKAL ASFISHQQMA
     SGFVGPANPG FCEAASLLGT SWDKGIFSWA CVNHELDNKH SFPTFSRTLP SPIRVLVTVM
     KYFQWAHAGV ISSDEDIWMH TANRVSSALR SQGLPVGVVL TSGRDSQSIQ KALQQIRQAD
     RIRIIIMCMH SALIGGETQT HFLELAHDLK MTDGTYVFVP YDVLLYSLPY KHSPYQVLRN
     NPKLREAYDA VLTITVESHE KTFYEAYAEA AARGEIPEKP DSNQVSPLFG TIYNSIYFIA
     QAMNNAMKKN GRASAASLVQ HSRNMQFYGF NQLIKTDSNG NGISEYVILD TNGKEWELRG
     TYTVDMETEL LRFRGTPIHF PGGRPTSADA KCWFAERKIC QGGIDPALAM MVCFALLIAL
     LSINGFAYFI RRRINKIQLI KGPNRILLTL EDVTFINPHF GSKRGSRASV SFQIISEVQS
     GRSPRLSFSS GSLTPATYEN SNIAIYEGDW VWLKKFPPGD FGDIKSIKSS ASDVFEMMKD
     LRHENVNPLL GFFYDSGMFA IVSEFCSRRS LEDILTNDDV KLDWMFKSSL LLDLIKGMKY
     LHHREFIHGR LKSRNCVVDG RFVLKVTDYG FNDILEMLRL SEEEPSEEEL LWTAPELLRA
     PGGIRLGSFA GDVYSFAIIM QEVMVRGAPF CMMDLPAKEI IDRLKMPPPV YRPVVSPEYA
     PAECLQLMKQ CWAEASEQRP TFDEIFNQFK TFNKGKKTNI IDSMLRMLEQ YSSNLEDLIR
     ERTEELEIEK QKTEKLLTQM LPLSVAESLK KGCTVEPEGF DLVTLYFSDI VGFTTISAMS
     EPIEVVDLLN DLYTLFDAII GSHDVYKVET IGDAYMVASG LPKRNGSRHA AEIANMSLDI
     LSSVGTFKMR HMPEVPVRIR IGLHSGPVVA GVVGLTMPRY CLFGDTVNTA SRMESTGLPY
     RIHVSLSTVT ILQTLSEGYE VELRGRTELK GKGTEETFWL VGKKGFTKPL PVPPPVGKDG
     QVGHGLQPAE IAAFQRRKAE RQLVRNKP
//