Editing ABC transporter (section)

{{short description|Gene family}}
{{Infobox protein family
| Symbol = ABC_tran
| Name = ABC Transporter, NBD
| image = 1l7v_opm.png
| width =
| caption = Vitamin B<sub>12</sub> transporter, BtuCD PDB {{PDBe|1l7v}}
| Pfam = PF00005
| Pfam_clan =
| InterPro = IPR003439
| SMART =
| PROSITE = PDOC00185
| MEROPS =
| SCOP = 1b0u
| TCDB = 3.A.1
| OPM family = 17
| OPM protein = 3g5u
| CAZy =
| CDD =
}}

[[Image:3b60.png|thumb|Lipid [[flippase]] MsbA]]
[[Image:2onk.png|thumb|[[Molybdate-transporting ATPase|Molybdate transporter]] AB<sub>2</sub>C<sub>2</sub> complex, open state]]

The '''ABC transporters''', '''ATP synthase (ATP)-binding cassette transporters'''  are a transport system superfamily that is one of the largest and possibly one of the oldest [[gene family|gene families]]. It is represented in all [[extant taxon|extant]] [[Phylum|phyla]], from [[prokaryote]]s to [[human]]s.<ref name=":0">{{Cite journal|last1=Fath|first1=M. J.|last2=Kolter|first2=R.|date=December 1993|title=ABC transporters: bacterial exporters|journal=Microbiological Reviews|volume=57|issue=4|pages=995–1017|issn=0146-0749|pmid=8302219|pmc=372944|doi=10.1128/MMBR.57.4.995-1017.1993}}</ref><ref name=Jones2004>{{cite journal | vauthors = Jones PM, George AM | title = The ABC transporter structure and mechanism: perspectives on recent research | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 6 | pages = 682–99 | date = Mar 2004 | pmid = 15052411 | doi = 10.1007/s00018-003-3336-9 | s2cid = 21422822 | pmc = 11138499 }}</ref><ref name= Ponte-SucreA>{{cite book | veditors = Ponte-Sucre A | year=2009 |title=ABC Transporters in Microorganisms | publisher=Caister Academic | isbn= 978-1-904455-49-3}}</ref> ABC transporters belong to [[translocase]]s.

ABC transporters often consist of multiple subunits, one or two of which are [[transmembrane protein]]s and one or two of which are membrane-associated [[AAA proteins|AAA]] [[ATPases]].{{Citation needed|date=December 2023}} The ATPase subunits utilize the energy of [[adenosine triphosphate]] (ATP) binding and hydrolysis to provide the energy needed for the translocation of substrates across membranes, either for uptake or for export of the substrate.

Most of the uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as [[RNA translation|translation of RNA]] and [[DNA repair]].<ref name="davidson">{{cite journal | vauthors = Davidson AL, Dassa E, Orelle C, Chen J | title = Structure, function, and evolution of bacterial ATP-binding cassette systems | journal = Microbiology and Molecular Biology Reviews | volume = 72 | issue = 2 | pages = 317–64, table of contents | date = Jun 2008 | pmid = 18535149 | pmc = 2415747 | doi = 10.1128/MMBR.00031-07 }}</ref><ref name="goffeau">{{cite book | editor1-last = Lane | editor1-first = William J. | editor2-last = Lennarz | editor2-first = M. Daniel | title = Encyclopedia of Biological Chemistry | pages = 7–11 | date = 2013 | publisher = Academic Press | location = London | isbn = 978-0-12-378631-9 | edition = Second | doi = 10.1016/B978-0-12-378630-2.00224-3 | chapter = ABC Transporters | vauthors = Goffeau A, de Hertogh B, Baret PV }}</ref> ABC transporters are considered to be an ABC superfamily based on the similarities of the sequence and organization of their ATP-binding [[Gene cassette|cassette]] (ABC) domains, even though the [[integral membrane protein]]s appear to have evolved independently several times, and thus comprise different protein families.<ref name="Wang2009">{{cite journal | vauthors = Wang B, Dukarevich M, Sun EI, Yen MR, Saier MH | title = Membrane porters of ATP-binding cassette transport systems are polyphyletic | journal = The Journal of Membrane Biology | volume = 231 | issue = 1 | pages = 1–10 | date = Sep 2009 | pmid = 19806386 | doi = 10.1007/s00232-009-9200-6 | pmc = 2760711 }}</ref> Like the ABC exporters, it is possible that the integral membrane proteins of ABC uptake systems also evolved at least three times independently, based on their high resolution three-dimensional structures.<ref>{{cite journal | vauthors = ter Beek J, Guskov A, Slotboom DJ | title = Structural diversity of ABC transporters | journal = The Journal of General Physiology | volume = 143 | issue = 4 | pages = 419–35 | date = Apr 2014 | pmid = 24638992 | doi = 10.1085/jgp.201411164 | pmc=3971661}}</ref> ABC uptake porters take up a large variety of nutrients, biosynthetic precursors, trace metals and [[vitamins]], while exporters transport [[lipid]]s, [[sterol]]s, [[drug]]s, and a large variety of primary and secondary metabolites.  Some of these exporters in humans are involved in tumor resistance, [[cystic fibrosis]] and a range of other inherited human diseases. High level expression of the genes encoding some of these exporters in both prokaryotic and eukaryotic organisms (including human) result in the development of resistance to multiple drugs such as antibiotics and anti-cancer agents.

Hundreds of ABC transporters have been characterized from both prokaryotes and eukaryotes.<ref name="Choi_2005">{{cite journal | vauthors = Choi CH | title = ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal | journal = Cancer Cell International | volume = 5 | pages = 30 | date = Oct 2005 | pmid = 16202168 | pmc = 1277830 | doi = 10.1186/1475-2867-5-30 | doi-access = free }}</ref> ABC genes are essential for many processes in the cell, and mutations in human genes cause or contribute to several human genetic diseases.<ref name="Dean_2001">{{cite journal | vauthors = Dean M, Hamon Y, Chimini G | title = The human ATP-binding cassette (ABC) transporter superfamily | journal = Journal of Lipid Research | volume = 42 | issue = 7 | pages = 1007–17 | date = Jul 2001 | doi = 10.1016/S0022-2275(20)31588-1 | pmid = 11441126 | doi-access = free }}</ref> Forty eight ABC genes have been reported in humans. Among these, many have been characterized and shown to be causally related to diseases present in humans such as [[cystic fibrosis]], [[adrenoleukodystrophy]], [[Stargardt disease]], drug-resistant tumors, [[Dubin–Johnson syndrome]], Byler's disease, progressive familiar intrahepatic cholestasis, X-linked [[sideroblastic anemia]], [[ataxia]], and persistent and hyperinsulimenic hypoglycemia.<ref name="Choi_2005"/> ABC transporters are also involved in [[multiple drug resistance]], and this is how some of them were first identified. When the ABC transport proteins are overexpressed in cancer cells, they can export anticancer drugs and render tumors resistant.<ref name="Lodish_2012">{{cite book | vauthors = Scott MP, Lodish HF, Berk A, Kaiser, C, Krieger M, Bretscher A, Ploegh H, Amon A | title = Molecular Cell Biology | publisher = W. H. Freeman | location = San Francisco | year = 2012 | isbn = 978-1-4292-3413-9 }}</ref>