A substrate-based ontology for human solute carriers.
SLCs
annotation
de-orphanization
ontology
solute carriers
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
22
04
2020
revised:
24
06
2020
accepted:
26
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
15
7
2021
Statut:
ppublish
Résumé
Solute carriers (SLCs) are the largest family of transmembrane transporters in the human genome with more than 400 members. Despite the fact that SLCs mediate critical biological functions and several are important pharmacological targets, a large proportion of them is poorly characterized and present no assigned substrate. A major limitation to systems-level de-orphanization campaigns is the absence of a structured, language-controlled chemical annotation. Here we describe a thorough manual annotation of SLCs based on literature. The annotation of substrates, transport mechanism, coupled ions, and subcellular localization for 446 human SLCs confirmed that ~30% of these were still functionally orphan and lacked known substrates. Application of a substrate-based ontology to transcriptomic datasets identified SLC-specific responses to external perturbations, while a machine-learning approach based on the annotation allowed us to identify potential substrates for several orphan SLCs. The annotation is available at https://opendata.cemm.at/gsflab/slcontology/. Given the increasing availability of large biological datasets and the growing interest in transporters, we expect that the effort presented here will be critical to provide novel insights into the functions of SLCs.
Identifiants
pubmed: 32697042
doi: 10.15252/msb.20209652
pmc: PMC7374931
doi:
Substances chimiques
Amino Acids
0
Membrane Transport Proteins
0
Banques de données
GEO
['GSE153034']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9652Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Mol Syst Biol. 2020 Jul;16(7):e9652
pubmed: 32697042
Nat Protoc. 2009;4(8):1184-91
pubmed: 19617889
Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6859-64
pubmed: 23569283
Bioinformatics. 2010 Oct 15;26(20):2647-8
pubmed: 20829444
Protein Sci. 2010 Mar;19(3):412-28
pubmed: 20052679
Nat Rev Drug Discov. 2016 Feb;15(2):143
pubmed: 26837595
Mol Aspects Med. 2013 Apr-Jun;34(2-3):95-107
pubmed: 23506860
Cancer Treat Rev. 2012 Oct;38(6):726-36
pubmed: 22342103
Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12
pubmed: 25348405
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Nat Rev Drug Discov. 2015 Aug;14(8):543-60
pubmed: 26111766
Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10988-E10997
pubmed: 30373828
Cell. 2015 Jul 30;162(3):478-87
pubmed: 26232220
PLoS Genet. 2015 Apr 07;11(4):e1005158
pubmed: 25849282
Nat Rev Drug Discov. 2020 Jul;19(7):429-430
pubmed: 32265506
Genome Biol. 2014;15(12):550
pubmed: 25516281
Mol Biol Cell. 2018 Dec 15;29(26):3183-3200
pubmed: 30354837
PLoS Genet. 2019 Sep 25;15(9):e1008208
pubmed: 31553721
Methods Mol Biol. 2017;1654:55-75
pubmed: 28986783
Amino Acids. 2009 May;37(1):79-88
pubmed: 19009228
Genome Res. 2016 Oct;26(10):1397-1410
pubmed: 27470110
Brief Bioinform. 2015 Nov;16(6):1069-80
pubmed: 25863278
Cell. 2013 Jul 18;154(2):403-15
pubmed: 23870128
J Nutr Biochem. 2013 Oct;24(10):1697-708
pubmed: 23643525
Front Pharmacol. 2018 Sep 07;9:1011
pubmed: 30245630
Trends Pharmacol Sci. 2017 Mar;38(3):305-315
pubmed: 27939446
Bioinformatics. 2005 Aug 15;21(16):3439-40
pubmed: 16082012
Cell Syst. 2018 Feb 28;6(2):230-244.e1
pubmed: 29428416
Science. 2018 Nov 16;362(6416):
pubmed: 30442778