Solute_carrier_family
Solute carrier family
Family of membrane transport proteins
The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families.[1][2] Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.
Solutes that are transported by the various SLC group members are extremely diverse and include both charged and uncharged organic molecules as well as inorganic ions and the gas ammonia.
As is typical of integral membrane proteins, SLCs contain a number of hydrophobic transmembrane alpha helices connected to each other by hydrophilic intra- and extra-cellular loops. Depending on the SLC, these transporters are functional as either monomers or obligate homo- or hetero-oligomers. Many SLC families are members of the major facilitator superfamily.
By convention of the nomenclature system, members within an individual SLC family have greater than 20-25% sequence identity to each other. In contrast, the homology between SLC families is very low to non-existent.[3] Hence, the criteria for inclusion of a family into the SLC group is not evolutionary relatedness to other SLC families but rather functional (i.e., an integral membrane protein that transports a solute).
The SLC group include examples of transport proteins that are:
- facilitative transporters (allow solutes to flow downhill with their electrochemical gradients)
- secondary active transporters (allow solutes to flow uphill against their electrochemical gradient by coupling to transport of a second solute that flows downhill with its gradient such that the overall free energy change is still favorable)
The SLC series does not include members of transport protein families that have previously been classified by other widely accepted nomenclature systems including:
- primary active transporters (allow flow uphill against electrochemical gradients) such as ABC (ATP Binding Cassette) transporters by coupling transport to an energy releasing event such as ATP hydrolysis
- ion channels
- aquaporins (water channels)
Most members of the SLC group are located in the cell membrane, but some members are located in mitochondria (the most notable one being SLC family 25) or other intracellular organelles.
Names of individual SLC members have the following format:[4]
where:
- SLC is the root name (SoLute Carrier)
- n = an integer representing a family (e.g., 1-52)
- X = a single letter (A, B, C, ...) denoting a subfamily
- m = an integer representing an individual family member (isoform).
For example, SLC1A1 is the first isoform of subfamily A of SLC family 1.
An exception occurs with SLC family 21[5] (the organic anion transporting polypeptide transporters), which for historical reasons have names in the format SLCOnXm where n = family number, X = subfamily letter, and m = member number.
While the HGNC only assign nomenclature to human genes, by convention vertebrate orthologs of these genes adopt the same nomenclature (e.g., VGNC-assigned orthologs of SLC10A1). For rodents, the case of the symbols differs from other vertebrates by using title case, i.e. Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene.
The following families are named under SLC:[6]
- high-affinity glutamate and neutral amino acid transporter[7]
- facilitative GLUT transporter[8]
- heavy subunits of heterodimeric amino acid transporters[9]
- bicarbonate transporter[10]
- sodium glucose cotransporter[11]
- sodium- and chloride-dependent sodium:neurotransmitter symporters[12]
- cationic amino acid transporter/glycoprotein-associated[13]
- Na+/Ca2+ exchanger[14]
- (SLC8A1, SLC8A2, SLC8A3)
- Na+/H+ exchanger[15]
- sodium bile salt cotransport[16]
- proton coupled metal ion transporter[17]
- electroneutral cation-Cl cotransporter[18]
- Na+-sulfate/carboxylate cotransporter[19]
- urea transporter[20]
- proton oligopeptide cotransporter[21]
- monocarboxylate transporter[22]
- vesicular glutamate transporter[23]
- vesicular amine transporter[24]
- folate/thiamine transporter[25]
- type III Na+-phosphate cotransporter[26]
- organic anion transporting[27]
- organic cation/anion/zwitterion transporter[28]
- Na+-dependent ascorbic acid transporter[29]
- Na+/(Ca2+-K+) exchanger[30]
- mitochondrial carrier[31]
- (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, UCP1(SLC25A7), UCP2(SLC25A8), UCP3(SLC25A9), SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46), SLC25A47, SLC25A48, MTCH1(SLC25A49), MTCH2(SLC25A50), SLC25A51, SLC25A52, SLC25A53
- multifunctional anion exchanger[32]
- fatty acid transport proteins[33]
- Na+-coupled nucleoside transport[34]
- facilitative nucleoside transporter[35]
- zinc transporter[36]
- copper transporter[37]
- vesicular inhibitory amino acid transporter[38]
- (SLC32A1)
- Acetyl-CoA transporter[39]
- (SLC33A1)
- type II Na+-phosphate cotransporter[40]
- nucleotide-sugar transporter[41]
- subfamily A (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5)
- subfamily B (SLC35B1, SLC35B2, SLC35B3, SLC35B4)
- subfamily C (SLC35C1, SLC35C2)
- subfamily D (SLC35D1, SLC35D2, SLC35D3)
- subfamily E (SLC35E1, SLC35E2A, SLC35E2B, SLC35E3, SLC35E4)
- subfamily F (SLC35F1, SLC35F2, SLC35F3, SLC35F4, SLC35F5)
- subfamily G (SLC35G1, SLC35G3, SLC35G4, SLC35G5, SLC35G6)
- proton-coupled amino acid transporter[42]
- sugar-phosphate/phosphate exchanger[43]
- System A & N, sodium-coupled neutral amino acid transporter[44]
- metal ion transporter[45]
- basolateral iron transporter[46]
- (SLC40A1)
- MgtE-like magnesium transporter
- Ammonia transporter[47][48]
- Na+-independent, system-L like amino acid transporter
- (SLC43A1, SLC43A2, SLC43A3)
- Choline-like transporter
- Putative sugar transporter
- Folate transporter
- multidrug and toxin extrusion
- Heme transporter family
- (SLC48A1)
- Heme transporter
- (FLVCR1(SLC49A1), FLVCR2(SLC49A2), SLC49A3, SLC49A4)
- Sugar efflux transporters of the SWEET family
- (SLC50A1)
- Transporters of steroid-derived molecules
- Riboflavin transporter family RFVT/SLC52
- Phosphate carriers
- Mitochondrial pyruvate carriers
- Mitochondrial cation/proton exchangers
- Sideroflexins
- (SFXN1(SLC56A1), SFXN2(SLC56A2), SFXN3(SLC56A3), SFXN4(SLC56A4), SFXN5(SLC56A5))
- NiPA-like magnesium transporter family
- (NIPA1(SLC57A1), NIPA2(SLC57A2), NIPAL1(SLC57A3), NIPAL2(SLC57A4), NIPAL3(SLC57A5), NIPAL4(SLC57A6))
- MagT-like magnesium transporter family
- Sodium-dependent lysophosphatidylcholine symporter family
- (MFSD2A(SLC59A1), MFSD2B(SLC59A2))
- Glucose transporters
- (MFSD4A(SLC60A1), MFSD4B(SLC60A2))
- Molybdate transporter family
- (MFSD5(SLC61A1))
- Pyrophosphate transporters
- (ANKH(SLC62A1))
- Sphingosine-phosphate transporters
- (SPNS1(SLC63A1), SPNS2(SLC63A2), SPNS3(SLC63A3))
- Golgi Ca2+/H+ exchangers
- (TMEM165(SLC64A1))
- NPC-type cholesterol transporters
- (NPC1(SLC65A1), NPC1L1(SLC65A2))
- Cationic amino acid exporters
- (SLC66A1, SLC66A2, SLC66A3, CTNS(SLC66A4), MPDU1(SLC66A5))
Putative SLCs, also called atypical SLCs, are novel, plausible secondary active or facilitative transporter proteins that share ancestral background with the known SLCs. [2][49] The atypical SLCs of MFS type can, however, be subdivided into 15 Putative MFS Transporter Families (AMTF).[49]
All the putative SLCs are plausible SLC transporters. Some are only "atypical" when it comes to their nomenclature; the genes have an SLC assignment but as an alias, and have retained their already assigned "non-SLC" gene symbol as the approved symbol.
Here are some Putative SLCs listed: OCA2, CLN3, TMEM104, SPNS1, SPNS2, SPNS3, SV2A, SV2B, SV2C, SVOP, SVOPL, MFSD1,[50] MFSD2A, MFSD2B, MFSD3,[50] MFSD4A,[51] MFSD4B, MFSD5,[52] MFSD6, MFSD6L, MFSD8, MFSD9,[51] MFSD10, MFSD11,[52] MFSD12, MFSD13A, MFSD14A,[53] MFSD14B,[53] UNC93A[54][55] and UNC93B1.
- Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (February 2004). "The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction". Pflügers Archiv. 447 (5): 465–468. doi:10.1007/s00424-003-1192-y. PMID 14624363. S2CID 1866661.
- Perland E, Fredriksson R (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences. 38 (3): 305–315. doi:10.1016/j.tips.2016.11.008. PMID 27939446.
- Höglund PJ, Nordström KJ, Schiöth HB, Fredriksson R (April 2011). "The solute carrier families have a remarkably long evolutionary history with the majority of the human families present before divergence of Bilaterian species". Molecular Biology and Evolution. 28 (4): 1531–1541. doi:10.1093/molbev/msq350. PMC 3058773. PMID 21186191.
- Hediger MA, Clémençon B, Burrier RE, Bruford EA (2013). "The ABCs of membrane transporters in health and disease (SLC series): introduction". Molecular Aspects of Medicine. 34 (2–3): 95–107. doi:10.1016/j.mam.2012.12.009. PMC 3853582. PMID 23506860.
- He L, Vasiliou K, Nebert DW (January 2009). "Analysis and update of the human solute carrier (SLC) gene superfamily". Human Genomics. 3 (2): 195–206. doi:10.1186/1479-7364-3-2-195. PMC 2752037. PMID 19164095.
- "SLCtables". slc.bioparadigms.org. Retrieved 2018-03-07.
- Uldry M, Thorens B (February 2004). "The SLC2 family of facilitated hexose and polyol transporters". Pflügers Archiv. 447 (5): 480–489. doi:10.1007/s00424-003-1085-0. PMID 12750891. S2CID 25539725.
- Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y (February 2004). "CATs and HATs: the SLC7 family of amino acid transporters" (PDF). Pflügers Archiv. 447 (5): 532–542. doi:10.1007/s00424-003-1086-z. PMID 14770310. S2CID 11670040.
- Orlowski J, Grinstein S (February 2004). "Diversity of the mammalian sodium/proton exchanger SLC9 gene family". Pflügers Archiv. 447 (5): 549–565. doi:10.1007/s00424-003-1110-3. PMID 12845533. S2CID 5691463.
- Hagenbuch B, Dawson P (February 2004). "The sodium bile salt cotransport family SLC10" (PDF). Pflügers Archiv. 447 (5): 566–570. doi:10.1007/s00424-003-1130-z. PMID 12851823. S2CID 35115446.
- Eiden LE, Schäfer MK, Weihe E, Schütz B (February 2004). "The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine". Pflügers Archiv. 447 (5): 636–640. doi:10.1007/s00424-003-1100-5. PMID 12827358. S2CID 20764857.
- Hagenbuch B, Meier PJ (February 2004). "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties" (PDF). Pflügers Archiv. 447 (5): 653–665. doi:10.1007/s00424-003-1168-y. PMID 14579113. S2CID 21837213.
- Murer H, Forster I, Biber J (February 2004). "The sodium phosphate cotransporter family SLC34" (PDF). Pflügers Archiv. 447 (5): 763–767. doi:10.1007/s00424-003-1072-5. PMID 12750889. S2CID 34041192.
- Boron WF (December 2010). "Sharpey-Schafer lecture: gas channels". Experimental Physiology. 95 (12): 1107–1130. doi:10.1113/expphysiol.2010.055244. PMC 3003898. PMID 20851859.
- Perland E, Bagchi S, Klaesson A, Fredriksson R (September 2017). "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression". Open Biology. 7 (9): 170142. doi:10.1098/rsob.170142. PMC 5627054. PMID 28878041.
- Perland E, Hellsten SV, Lekholm E, Eriksson MM, Arapi V, Fredriksson R (February 2017). "The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake". Journal of Molecular Neuroscience. 61 (2): 199–214. doi:10.1007/s12031-016-0867-8. PMC 5321710. PMID 27981419.
- Perland E, Hellsten SV, Schweizer N, Arapi V, Rezayee F, Bushra M, Fredriksson R (2017). "Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice". PLOS ONE. 12 (10): e0186325. Bibcode:2017PLoSO..1286325P. doi:10.1371/journal.pone.0186325. PMC 5648162. PMID 29049335.
- Perland E, Lekholm E, Eriksson MM, Bagchi S, Arapi V, Fredriksson R (2016). "The Putative SLC Transporters Mfsd5 and Mfsd11 Are Abundantly Expressed in the Mouse Brain and Have a Potential Role in Energy Homeostasis". PLOS ONE. 11 (6): e0156912. Bibcode:2016PLoSO..1156912P. doi:10.1371/journal.pone.0156912. PMC 4896477. PMID 27272503.
- Lekholm E, Perland E, Eriksson MM, Hellsten SV, Lindberg FA, Rostami J, Fredriksson R (2017). "Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability". Frontiers in Molecular Neuroscience. 10: 11. doi:10.3389/fnmol.2017.00011. PMC 5263138. PMID 28179877.
- Ceder MM, Lekholm E, Hellsten SV, Perland E, Fredriksson R (2017). "The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice". Frontiers in Molecular Neuroscience. 10: 351. doi:10.3389/fnmol.2017.00351. PMC 5671512. PMID 29163028.
- Ceder MM, Aggarwal T, Hosseini K, Maturi V, Patil S, Perland E, et al. (2020). "CG4928 Is Vital for Renal Function in Fruit Flies and Membrane Potential in Cells: A First In-Depth Characterization of the Putative Solute Carrier UNC93A". Frontiers in Cell and Developmental Biology. 8: 580291. doi:10.3389/fcell.2020.580291. PMC 7591606. PMID 33163493.
SLC Tables. SLCtables