ABCMdb

ABCA4 p.Thr446Ala

Predicted by SNAP2:	A: N (61%), C: N (53%), D: N (57%), E: N (61%), F: D (63%), G: N (53%), H: N (72%), I: N (57%), K: N (72%), L: N (53%), M: N (57%), N: N (72%), P: N (53%), Q: N (61%), R: N (61%), S: N (82%), V: N (61%), W: D (75%), Y: D (59%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, V: N, W: D, Y: N,

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Publications
[hide] Membrane topology of the ATP binding cassette tran... J Biol Chem. 2001 Jun 29;276(26):23539-46. Epub 2001 Apr 24. Bungert S, Molday LL, Molday RS
Membrane topology of the ATP binding cassette transporter ABCR and its relationship to ABC1 and related ABCA transporters: identification of N-linked glycosylation sites.
J Biol Chem. 2001 Jun 29;276(26):23539-46. Epub 2001 Apr 24., [PMID:11320094]

Abstract [show]
ABCR is a member of the ABCA subclass of ATP binding cassette transporters that is responsible for Stargardt macular disease and implicated in retinal transport across photoreceptor disc membranes. It consists of a single polypeptide chain arranged in two tandem halves, each having a multi-spanning membrane domain followed by a nucleotide binding domain. To delineate between several proposed membrane topological models, we have identified the exocytoplasmic (extracellular/lumen) N-linked glycosylation sites on ABCR. Using trypsin digestion, site-directed mutagenesis, concanavalin A binding, and endoglycosidase digestion, we show that ABCR contains eight glycosylation sites. Four sites reside in a 600-amino acid exocytoplasmic domain of the N-terminal half between the first transmembrane segment H1 and the first multi-spanning membrane domain, and four sites are in a 275-amino acid domain of the C half between transmembrane segment H7 and the second multi-spanning membrane domain. This leads to a model in which each half has a transmembrane segment followed by a large exocytoplasmic domain, a multi-spanning membrane domain, and a nucleotide binding domain. Other ABCA transporters, including ABC1 linked to Tangier disease, are proposed to have a similar membrane topology based on sequence similarity to ABCR. Studies also suggest that the N and C halves of ABCR are linked through disulfide bonds.

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No. Sentence Comment
58 ABCR(⌬8) had mutations in eight N-linked glycosylation sites within two ECDs at the following positions: Asn-98 (S100A), Asn-415 (T417A), Asn-444 (T446A), Asn-504 (T506A), Asn-1469 (T1471A), Asn-1529 (S1531A), Asn-1588 (S1590A), and Asn-1662 (T1664A) as shown in Fig. 2. Login to comment
153 TABLE I N-linked glycosylation mutants Protein N-Linked glycosylation sites Mutations ABCR(WT) Asn-98, Asn-415, Asn-444, Asn-504 None Asn-1469, Asn-1529, Asn-1588, Asn-1662 ABCR(⌬8) None S100A, T417A, T446A, T506A T1471A, S1531A, S1590A, T1664A ABCR(⌬4N) Asn-1469, Asn-1529, Asn-1588, Asn-1662 S100A, T417A, T446A, T506A ABCR(⌬4C) Asn-98, Asn-415, Asn-444, Asn-504 T1471A, S1531A, S1590A, T1664A ABCR(⌬7-N1469) Asn-1469 S100A, T417A, T446A, T506A T1471A, S1531A, S1590A S100A, T417A, T446A, T506A ABCR(⌬7-N1529) Asn-1529 T1471A, S1531A, T1664A S100A, T417A, T446A, T506A ABCR(⌬7-N1588) Asn-1588 T1471A, S1590A, T1664A ABCR(⌬7-N1662) Asn-1662 S100A, T417A, T446A, T506A S1531A, S1590A, T1664A N-tr-ABCR (WT) Asn-98, Asn-415, Asn-444, Asn-504 None N-tr-ABCR(⌬4) None S100A, T417A, T446A, T506A N-tr-ABCR(⌬3-N98) Asn-98 T417A, T446A, T506A N-tr-ABCR(⌬3-N415) Asn-415 S100A, T446A, T506A N-tr-ABCR(⌬3-N444) Asn-444 S100A, T417A, T506A N-tr-ABCR(⌬3-N504) Asn-504 S100A, T417A, T446A DISCUSSION Membrane Topology and Structural Features of ABCR- Computer-derived hydropathy profiles and comparative protein analysis serve as a useful starting point in developing working models for the topology of novel membrane proteins. Login to comment
57 ABCR(èc;8) had mutations in eight N-linked glycosylation sites within two ECDs at the following positions: Asn-98 (S100A), Asn-415 (T417A), Asn-444 (T446A), Asn-504 (T506A), Asn-1469 (T1471A), Asn-1529 (S1531A), Asn-1588 (S1590A), and Asn-1662 (T1664A) as shown in Fig. 2. Login to comment