Retina International's Scientific Newsletter

	Retina International's Scientific Newsletter
Editor's Notes from literature on Guanylate Cyclase (RetGC)

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)

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)

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)

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)

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)

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

Glu 925 Cys together with Cys 995 Asp change substrate specificity from GTP to ATP

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

Immunoreactivity in ROS, INL, and ONL

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. F�lle, 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., F�lle, 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