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Editor's Notes

from literature on

Guanylate Cyclase (RetGC)

Editor's Notes

Recent update from: 19.12.1999


GUC2D Notes

  • Catalyzes generation of cGMP from GTP
  • Insensitive to hormones
  • Varies between being totally soluble to being totally particulate
  • Mn2+ is preferred activating ion
  • Soluble GC exhibits cooperative kinetic
  • Particulate GC exhibits linear kinetic
Species:
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (10)


GUC2D Notes

  • IR in particulate fraction
  • Particulate fraction belongs to photoreceptors
Species:
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (4)


GC Notes

  • GC (EC 4.6.1.2)
  • Particulate that is Ca2+ activated in Bovine ROS and inhibited by PRKC inhibition
Species:
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (24)


GC Notes

  • Cytoplasmic GCs are NOS sensitive
  • Membrane bound GCs are peptide induced
  • Cytoplasmic bound forms contain a und b subunits -> RetGC is membrane bound
  • Cytoplasmic shows no homodimer activity
  • Cytoplasmic GCs contains heme (in the aminoterminal part of FixL)
Species:
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (9)


GC Notes

  • Four structural motifs: extracellular ligand binding, transmembrane, intracellular protein kinase and catalytic
  • ATP enhances GC activity 2-fold
  • ATP binds GC at a site distinct from GTP-binding site
  • ATP effect is lost on solubilization
  • Kinase activity is Mg2+-dependent
  • Kinase domain autophospohrylates Ser residues
  • Kinase is unaffected by Ca2+, cyclic nucleotides, and some lipids
  • ATP-stimulation is light- and Ca2+-independent
Species: Bos taurus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (2)


GUC2D Notes

  • Bovine RosGC = RetGC = GUC2D
Species: Bos taurus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (7)


GC Notes

  • Integral membrane GC: Rho equals 1:440
  • Forms homooligomers as dimers to tetramers
  • C-terminus is characteristic to membrane receptor GC family
Species: Bos taurus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE: 115 kDa

calculated:
Reference: (2)


GUC2D Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids: 1108 AA
Molecularweight on SDS-PAGE:

calculated:
Reference: (21)


GC-2 Notes

  • Present in outer segments
  • Activated by GCAP2
Species: Homo sapiens
See also: GCAP
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids: 1108 AA
Molecularweight on SDS-PAGE:

calculated:
Reference: (22)


GUC1B3 Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man: 4q31.3-q33

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


GC-E Notes

  • Substantial reduction of cone ERG in a GC-E knockout
  • Loss of cone cells
  • ERG of knockout different from LCA patients
Species: Mus musculus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (3)


GC Notes

  • Expressed in retina in two isoforms GC-E and GC-F
  • An artificial mutation of GC-E (D878A) act as a dominant negative regulator of native activity of both isoforms
  • Homomers and heteromers could be formed but the vast majority forms homomers
  • IR is enhanced in ROS
  • No label in the connecting cilium
  • Cyclase activity was found in a 240 - 480 kDa complex
Species: Rattus norvegicus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (27)


GUC2D Notes

Species: recombinant
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (23)


NPR2, brain Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man: 9p12-p21

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


NPR1, brain Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man: 1q21-q22

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


GC-A, brain Notes

Species: Rattus norvegicus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data
cDNA:
Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (14)


GC-1, cone Notes

  • Present in outer segments
  • Activated by GCAP1 and 2
Species: Homo sapiens
See also: GCAP
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids: 1103 AA
Molecularweight on SDS-PAGE:

calculated:
Reference: (22)


GC-E, eye Notes

Species: Mus musculus
See also:
Chromosomal localisation in man:

in mouse: 11
Gene Data

Exons: 19
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (26)


GC-F, eye Notes

  • 4 domains: extracellular, transmembrane, catalytic, protein kinase like
  • eye specific
  • ORF predicts 1108 AA precursor protein
  • 50 AA signal sequence
  • IP=6.6
  • membrane bound
  • amino acid similarity to bovine retGC 30% (GC-F)
Species: Rattus norvegicus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data
mRNA: 11 kb
Exons:
Primers:
Protein Data
Aminoacids: 1058 AA
Molecularweight on SDS-PAGE: 119 kDa

calculated:
Reference: (25)


GC-E, eye Notes

  • In eye and pineal gland
  • GC-E most similar to retGC =? rat homologue
  • potential glycosylation site in the extracellular domain
  • ORF predicts 1108 AA precursor protein
  • 54 bp signal sequence
  • IP=7.1
  • Membrane bound
  • Amino acid similarity to bovine retGC 84% (GC-E)
Species: Rattus norvegicus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data
mRNA: 8.5 kb
Exons:
Primers:
Protein Data
Aminoacids: 1054 AA
Molecularweight on SDS-PAGE: 115 kDa

calculated:
Reference: (25)


GC, membrane Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data
cDNA:
Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE: 112 kDa

calculated:
Reference: (6)


NPRa, NPRa Notes

Species: Mus musculus
See also:
Chromosomal localisation in man:

in mouse: 3
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (20)


retGC, particulate Notes

  • Bovine 112 kDa = particulate GC = membrane bound
  • 100% identical to human retGC
  • N-linked glycosylation of high mannose type
  • Ca2+ controlled
  • retGC transcripts in cell bodies and inner segments
  • Soluble forms are heterodimeric NO sensitive hemeproteins
Species: Bos taurus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (12)


GC-A, particulate Notes

  • Expressed predominantly in rods
  • Indication of multiple regulatory pathways for cGMP level control in rods
  • GC-A identical to kidney and testis form is expressed in retina
  • GC-B form brain specific, not in retina
Species: Rattus norvegicus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (1)


GC, retinal Notes

  • Axoneme associated enzyme
  • Highly cooperative Ca-switch, senses Ca in submicromolor range
  • Stimulated by regulator protein at low Ca2+
Species:
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (13)


ROSGC, retinal Notes

Species: Bos taurus
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE: 115 kDa

calculated:
Reference: (28)


GUC2D, retinal Notes

  • Particulate = membrane bound
  • 1 big subunit
  • N-terminal transmembrane domain
  • C-terminal catalytic
Species: Homo sapiens
See also:
Chromosomal localisation in man: 17p13.1

in mouse:
Gene Data

Exons: 4
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


RetGC, retinal Notes

  • RetGC predominantly in the photoreceptor layer
  • Small amount of RetGC in various other retinal cells
  • Higher immunostain in cone cells
  • In outer segments localized exclusively to membrane-rich domains
  • Associated with marginal region of disc- and/or plasma membrane
Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (16)


GUC2D, retinal Notes

  • RetGC2 regulated by Ca2+ and p24 = GCAP2
  • 2 RetGC
  • RetGC1 not Ca2+ sensitive
Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (5)


GUC2D, retinal Notes

  • Mutations in LCA
  • Marker D17S96 and D17S804
Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (18)


GUC2D, retinal Notes

  • Anti-RetGC labelled ROS and stronger COS disk membranes and plasmamembranes
  • Maybe two types of RetGC due to different labelling patterns
Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (15)


Ret-GC2, retinal, type 2 Notes

  • Genomic organization similar to Ret-GC1
  • More than 45 kb genomic size
Species: Homo sapiens
See also:
Chromosomal localisation in man: Xq22

in mouse:
Gene Data

Exons: 19
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (8)


GC, rod Notes

  • RHO:Cyclase = 1:104
  • Coverts GTP to cGMP + PPi
  • Ca2+ activated
  • 2 - 5 nmol cGMP/min/mg protein
  • Equimolar to phosphodiesterase
  • Axoneme-associated enzyme
Species: Bos taurus
See also: RHO
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated: 112000
Reference: (11)


NPR3, soluble Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man: 5p13-p14

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


GUC1A3, soluble Notes

Species: Homo sapiens
See also:
Chromosomal localisation in man: 4q31.3-q33

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids:
Molecularweight on SDS-PAGE:

calculated:
Reference: (19)


RetGC2, type 2 Notes

  • 50 AA signal peptide
  • No N-linked glycosylation site
  • activated by p24 (GCAP2)
  • inhibited by Ca2+
  • RNA in inner segments and ONL predominantly in COS
  • IR not possible in situ
Species: Homo sapiens
See also:
Chromosomal localisation in man:

in mouse:
Gene Data

Exons:
Primers:
Protein Data
Aminoacids: 1058 AA
Molecularweight on SDS-PAGE:

calculated: 119089
Reference: (17)


References:

1. Ahmads, I., Korbmacher, C., Segal, A.S., Cheung, P., Boulpaep, E.L., and Barnstable, C.J. Mouse cortical collecting duct cells show nonselective cation channel activity and express a gene related to the cGMP-gated rod photoreceptor channel. 1992; Proc.Natl.Acad.Sci.U.S.A. 89: 10262 - 10266.
Goto Top

2. Aparicio, J.G. and Applebury, M.L. The bovine photoreceptor outer segment guanylate cyclase: purification, kinetic properties, and molecular size. 1995; Protein Expr.Purif. 6: 501 - 511.
Goto Top

3. Birch, D.G., Yang, R.B., and Garbers, D.-L. Detectable Responses To Light In Guanylyl Cyclase (GC-E) Deficient Mice. 1998; Invest.Ophthalmol.Vis.Sci. 39: S643
Goto Top

4. De Vries, G.W. and Ferrendelli, J.A. Characterization and localization of adenylate and guanylate cyclases. 1982; Methods.Enzymol. 81: 517 - 522.
Goto Top

5. Dizhoor, A.M., Olshevskaya, E.V., and Hurley, J.B. A novel retinal Ca2+-binding protein, p24, stimualtes photoreceptor guanylyl cyclase and associates with the outer segment membranes in a calcium-sensitive manner. 1995; Invest.Ophthalmol.Vis.Sci. 36: S223
Goto Top

6. Duda, T., Goraczniak, R.M., and Sharma, R.K. Core sequence of ATP regulatory module in receptor guanylate cyclases. 1993; FEBS Lett. 315: 143 - 148.
Goto Top Link to PudMed

7. Duda, T., Goraczniak, R.M., Sitaramayya, A., and Sharma, R.K. Cloning of a photoreceptor guanylate cyclase. 1994; Invest.Ophthalmol.Vis.Sci. 35 (Suppl.): 1463
Goto Top

8. Fülle, H.J., Belonogoff, V., Wright, A.F., and Swaroop, A. Retinal Guanylate Cyclase-2: Genomic Organization and Possible Role in X-linked Retinitis Pigmentosa. 1998; Invest.Ophthalmol.Vis.Sci. 39: S300
Goto Top

9. Garbers, D.L. and Lowe, D.G. Guanylyl cyclase receptors. 1994; J.Biol.Chem. 269: 30741 - 30744.
Goto Top

10. Goldberg, N.D. and Haddox, M.K. Cyclic GMP metabolism and involvement in biological regulation. 1977; Ann.Rev.Biochem. 46: 823 - 896.
Goto Top

11. Koch, K.W. Purification and identification of photoreceptor guanylate cyclase. 1991; J.Biol.Chem. 266: 8634 - 8637.
Goto Top

12. Koch, K.W., Stecher, P., and Kellner, R. Bovine retinal rod guanyl cyclase represents a new N-glycosylated subtype of membrane-bound guanyl cyclases. 1994; Eur.J.Biochem. 222: 589 - 595.
Goto Top

13. Koch, K.W. and Stryer, L. Highly cooperative feedback control of retinal rod guanylate cyclase by calcium ions. 1988; Brain.Dev. 334: 64 - 66.
Goto Top

14. Kutty, R.K., Fletcher, R.T., Chader, G.J., and Krishna, G. Expression of guanylate cyclase-A mRNA in the rat retina: detection using polymerase chain reaction. 1992; Biochem.Biophys.Res.Comm. 182: 851 - 857.
Goto Top

15. Liu, X., Nishizawa, Y., Yamazaki, A., Wakabayashi, T., and Usukura, J. Immunocytochemical characterization of retinal guanylate cyclase in human and monkey retinas. 1995; Invest.Ophthalmol.Vis.Sci. 36: S222
Goto Top

16. Liu, X., Seno, K., Nishizawa, Y., Hayashi, F., Yamazaki, A., Matsumoto, H., Wakabayashi, T., and Usukura, J. Ultrastructural localization of retinal guanylate cyclase in human and monkey retinas. 1994; Exp.Eye Res. 59: 761 - 768.
Goto Top Link to PudMed

17. Lowe, D.G., Dizhoor, A.M., Liu, K., Gu, Q.M., Spencer, M., Laura, R., Lu, L., Hurley, J.B., and Gu, Q. Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. 1995; Proc.Natl.Acad.Sci.U.S.A. 92: 5535 - 5539.
Goto Top Link to PudMed

18. Loyer, M., Peschlow, A., Robitaille, J., Traboulsi, E., Little, J., Polomeno, R., Maumenee, I., Kaplan, J., and Koenekoop, R. Mutations In The Gene For Retinal Guanylate Cyclase In Patients With Leber's Congenital Amaurosis. 1997; Invest.Ophthalmol.Vis.Sci. 38: S680
Goto Top

19. Oliveira, L., Miniou, P., Viegas-Pequignot, E., Rozet, J.M., Dollfus, H., Pittler, S.J., and Viegas Pequignot, E. Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1 Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1. 1994; Genomics. 22: 478 - 481.
Goto Top Link to PudMed

20. Pandey, K.N., Adamson, M.C., Gu, Y.C., and Kozak, C.A. Genetic mapping of the gene encoding guanylate cyclase-A/atrial natriuretic factor receptor (Npra) to mouse chromosome 3. 1994; Mammalian.Genome. 5: 520 - 522.
Goto Top

21. Shyjan, A.W., de Sauvage, F.J., Gillett, N.A., Goeddel, D.V., and Lowe, D.G. Molecular cloning of a retina-specific membrane guanylyl cyclase. 1992; Neuron. 9: 727 - 737.
Goto Top

22. Surgucheva, I., Dizhoor, A., Hurley, J.B., Palczewski, K., and Baehr, W. Expression And Characterization Of Photoreceptor Guanylate Cyclases 1 And 2. 1997; Invest.Ophthalmol.Vis.Sci. 38: S477 - A1000.
Goto Top

23. Tucker, C.L., Miller, T.R., and Hurley, J. Mutagenesis Of The Catalytic Domain Of Retinal Guanylyl Cyclase (RETGC-1) Alters Substrate Specificity From GTP To ATP. 1998; Invest.Ophthalmol.Vis.Sci. 39: S953
Goto Top

24. Wolbring, G. and Schnetkamp, P.P. Activation by PKC of the Ca(2+)-sensitive guanylyl cyclase in bovine retinal rod outer segments measured with an optical assay. 1995; Biochemistry. 34: 4689 - 4695.
Goto Top Link to PudMed

25. Yang, R.B., Foster, D.C., Garbers, D.L., and Fulle, H.J. Two membrane forms of guanylyl cyclase found in the eye. 1995; Proc.Natl.Acad.Sci.U.S.A. 92: 602 - 606.
Goto Top

26. Yang, R.B., Fülle, H.J., and Garbers, D.L. Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina. 1996; Genomics. 31: 367 - 372.
Goto Top Link to PudMed

27. Yang, R.B. and Garbers, D.L. Two eye guanylyl cyclases are expressed in the same photoreceptor cells and form homomers in preference to heteromers. 1997; J.Biol.Chem. 272: 13738 - 13742.
Goto Top

28. Yoshida, A., Cooper, N.G.F., Liu, L., Pozdnyakov, N., and Sitaramayya, A. Localization of photoreceptor membrane guanylate cyclase. 1995; Invest.Ophthalmol.Vis.Sci. Suppl. S270
Goto Top


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Contact the editor: irpamp@irpa.org
This site is maintained and edited by
Dr. rer. medic. Markus Preising, Dipl.Biol.
Molecular Genetics Laboratory
Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics
University of Regensburg
Head: Prof. Dr. med. Birgit Lorenz