Retina International's Scientific Newsletter - ATP-binding Cassette Transporter Retina

	Retina International's Scientific Newsletter
Editor's Notes from literature on ATP-binding Cassette Transporter Retina (ABCR)

Recent update from: 18.12.1999

ABCR

Notes

at-, 11-cis and 13-cis RAl stimulates ATPase activity of ABCR
Retinoids and, most likely RAl, are the natural substrates for transport by ABCR in ROS
ATPase activity sensitive to surrounding lipids in membrane; PE activates, PC does not
ABCR shows uncompetitive stimulation by atRAl thus impliyng transport of atRAl
Thus STGD is a result of accumulation of atRAL or its derivates in ROS
On light flashes atRAl accumulates in ROS without accumulation of other retinoids
In ROS ABCR may act to flip PE-atRAl from the lumenal to the cytosolic side of disc membranes
Disruption of flipping results in accumulation of PE-atRAL in the lumen which is not possible in COS
PE-atRAl is converted to A2E in RPE afterwards

Species: Bos taurus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (8)

ABCR, RmP

Notes

Membrane-bound glycosylated protein in ROS
Member of the ATP-binding transporter family

Species: Bos taurus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (9)

ABCR, RmP

Notes

Glycoprotein
Specifically expressed in photoreceptors and outer segments
Unknown function
Phosphorylated
12 transmembrane segments
2 hydrophobic domains
2 ATP-binding motifs
Walker-B motif
3 sites for N-linked glycosylation
RmP/RHO ratio higher in frog than in bovine due to number of disc incisures of bovine
Control of free Ca²⁺?

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)

ABCR, RmP

Notes

Member of the ATP transporter family
Equal to large intrinsic membrane protein
Continually produced and secreted
Localized to the rims of frog retina
Role in structural froming of the disk structure
phosphorylated in light
Genebank entries of homologous fragments

Species: Bos taurus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: ca. 210 kDa
	calculated:

Reference: (9)

ABCR, RmP

Notes

2 tandemly arranged halfes
40 - 50% identity to ABC1 and ABC2
Binds ATP and GTP
Contains minimum of 1 carbohydrate chain
Distributed along the rim region of disc incisures
Mammalian homologue of frog photoreceptor rim protein
IR only in ROS
No stochiometric asssociation to an other protein
Residue Asn 1586 is likely to be glycosylated

Species: Bos taurus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids: 2264+16 AA

Molecularweight	on SDS-PAGE: 220 kDA
	calculated: 257 kDa

Reference: (6)

ABCR

Notes

High degree of conservation among the members of the ABC-superfamily splice sites
870 bp 5' were analysed
Expressed only in ROS
Flanking markers: D1S3361 - D1S236
Exon 30 alternatively spliced
Splice sites listed
Promotor sequence
Elements:
- AIRS (-762)
- Nrl-like (-708)
- Mash-1 (-655)
- Ret-4 (-489)
- RAR/RXR (-269)
- CRX/T_alpha (-33)
- TATA (-33)
Sites at -762, -708, and -662 suggest tissue-specific expression module

Species: Homo sapiens

See also:

Chromosomal localisation	in man: 1p22.3-22.2
	in mouse:

Gene Data

cDNA: 8184 bp

Exons: 51

Primers: GDB: 9300763 - 9300827

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (1)

ABCR

Notes

Hypothesis: ABCR cause different of phenotypes due to kind of mutation
STGD = heterozygous mutations or two mutations with residual activity
RP = two null mutations
CRD = combination of null and residual activity mutations
Frequency of heterozygotes: 0.02

Species: Homo sapiens

See also:

Chromosomal localisation	in man: 1p21-13
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (4)

ABCR

Notes

Markers: D1S2206, D1S2868, D1S236

Species: Homo sapiens

See also:

Chromosomal localisation	in man: 1p21-13
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (7)

ABCR

Notes

ca. 150 kb genomic DNA
Cryptic 3' splice site in exon 30

Species: Homo sapiens

See also:

Chromosomal localisation	in man: 1p22.1
	in mouse:

Gene Data

Exons: 50

Primers: Complete

Protein Data

Aminoacids: 2273 AA

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (5)

ABCR

Notes

Persons tested: 167 AMD (A); 220 controls (C), 98 STGD (S); 96 definitely unaffected (U)
Mutations: Asp 2177 Asn 7 A - 1 C - 0 U - 0 S; Asp 1961 Glu 6 A - 0 C - 0 U - 8 S; Glu 1704 Lys A + S
Heterozygotes: Ala 1038 Val/Arg 943 Trp
6519del11bp A + S

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (3)

ABCR, RmP

Notes

Expressed in photoreceptors, predominantly in outer segments
Membrane glycoprotein
Unknown function, may represent the the electron-dense filaments at the disc rim spanning the cytoplasmic space between disc rim and plasma membrane
Phosphorylated in light-dependent fashion
12 transmembrane segments, 2 transporter motifs, 2 nucleotide binding sites, 1 Walker B motif, 2 PKA/PKC phosphorylation sites within transporter motif
Hypothesis: divalent ion transport (Ca, Mg)

Species: Mus musculus

See also:

Chromosomal localisation	in man:
	in mouse: 3

Gene Data

mRNA: 7.3 kb

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 210 kDa
	calculated:

Reference: (2)

ABCR

Notes

4.0 kb deletion results in no abnormal histology
ERG: dark adaptation is normal

Species: Mus musculus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (10)

References:

1. Allikmets, R., Wasserman, W.W., Hutchinson, A., Smallwood, P., Nathans, J., Rogan, P.K., Schneider, T.D., and Dean, M. Organization of the ABCR gene: analysis of promoter and splice junction sequences. 1998; Gene. 215: 111 - 122.
Goto Top Link to PudMed

2. Azarian, S.M. and Travis, G.H. The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR). 1997; FEBS Lett. 409: 247 - 252.
Goto Top Link to PudMed

3. Bernstein, P.S., Zabriskie, N.A., Peiffer, A., Lupski, J.R., Dean, M., and Leppert, M. ABCR Mutations In Kindreds With Stargardt's Disease And Age-Related Macular Degeneration. 1998; Invest.Ophthalmol.Vis.Sci. 39: S900
Goto Top

4. Cremers, F.P.M., van de Pol, T.J.R., van Driel, M., den Hollander, A.I., van Haren, F.J.J., Knoers, N.V.A.M., Tijmes, N., Bergen, A.A.B., Rohrschneider, K., Blankenagel, A., Pinckers, A.J.G.L., Deutman, A.F., and Hoyng, C.B. Autosomal Recessive Retinitis Pigmentosa And Cone-Rod Dystrophy Caused By Splice Site Mutations In The Stargardt's Disease Gene ABCR. 1998; Invest.Ophthalmol.Vis.Sci. 39: S915
Goto Top

5. Gerber, S., Rozet, J.M., Vandepol, T.J.R., Hoyng, C.B., Munnich, A., Blankenagel, A., Kaplan, J., and Cremers, F.P.M. Complete Exon-Intron Structure Of The Retina-Specific ATP Binding Transporter Gene (ABCR) Allows The Identification Of Novel Mutations Underlying Stargardt-Disease. 1998; Genomics. 48: 139 - 142.
Goto Top

6. Illing, M., Molday, L.L., and Molday, R.S. The 220-kDa rim protein of retinal rod outer segments is a member of the ABC transporter superfamily. 1997; J.Biol.Chem. 272: 10303 - 10310.
Goto Top Link to PudMed

7. Shroyer, N.F., Singh, N., Allikmets, R., Hutchinson, A., Peiffer, A., Li, Y., Lupski, J.R., Dean, M., Leppert, M., and Lewis, R.A. Genotype/Phenotype Analysis Of A Retinal Specific ABC Transporter Gene, ABCR, In Stargardt Disease. 1998; Invest.Ophthalmol.Vis.Sci. 39: S900
Goto Top

8. Sun, H., Molday, R.S., and Nathans, J. Retinal Stimulates ATP Hydrolysis by Purified and Reconstituted ABCR, the Photoreceptor-specific ATP-binding Cassette Transporter Responsible for Stargardt Disease. 1999; J.Biol.Chem. 274: 8269 - 8281.
Goto Top Link to PudMed

9. Thomson, J.L., Brzeski, H., Dunbar, B., Forrester, J.V., Fothergill, J.E., and Converse, C.A. Photoreceptor Rim Protein: Partial Sequences Of cDNA Show A High Degree Of Similarity To ABC Transporters. 1997; Current.Eye Research. 16: 741 - 745.
Goto Top

10. Weng, J., Azarian, S.M., and Travis, G.H. Generation Of Mice With A Null Mutation In The Rim Protein RMP Gene (ABCR): An Animal Model For Recessive Stargardt's Disease. 1998; Invest.Ophthalmol.Vis.Sci. 39: S643
Goto Top

	Return to Retina International's Scientific Newsletter	Return to pagehead
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