Solute carrier family

The SoLute Carrier (SLC) group of membrane transport proteins include over 300 members organized into 47 families.cite journal |author=Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA|title=The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins: Introduction|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 465–8 |year= 2004| doi = 10.1007/s00424-003-1192-y |pmid= 14624363] The SLC gene nomenclature system was originally proposed by the Human Genome Organization (HUGO) and is the basis for the official HUGO 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 extraordinarily diverse and include both charged and uncharged organic molecules as well as inorganic ions.

As is typical of integral membrane proteins, SLCs contain a number of hydrophobic transmembrane alpha helices connected to each other by hydrophilic intra- or extra-cellular loops. Depending on the SLC, these transporters are functional as either monomers or obligate homo- or hetero-olgiomers.

cope

By convention of the nomenclature system, members within an individual SLC family have greater than 20-25% sequence homology to each other. In contrast, the homology between SLC families is very low to non-existent. 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 which 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 which 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)

ubcellular distribution

Most members of the SLC group are located in the outer cell membrane, but some members are located in mitochondria (most notably SLC family 25) or other intracellular organelles.

Nomenclature system

Names of individual SLC members have the following format:
* SLCnXmwhere:
* SLC is the root name (SoLute Carrier)
* n = an integer representing a family ("e.g.", 1-47),

* X = a single letter (A, B, C, ...) denoting a subfamily, and

* m = an integer representing an individual family member (isoform).

For example gene|SLC1A1 is the first isoform of subfamily A of SLC family 1.

An exception occurs with SLC family 21 (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 HUGO nomenclature system by definition only includes human genes, the nomenclature system has been informally extended to include rodent species through the use of lower cases letters ("e.g.", Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene).

Families

* (1) high affinity glutamate and neutral amino acid transportercite journal |author=Kanai Y, Hediger MA|title=The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 469–479 |year= 2004|doi= 10.1007/s00424-003-1146-4 |pmid= 14530974]
** (SLC1A1, SLC1A2, SLC1A3, SLC1A4, SLC1A5, SLC1A6, SLC1A7)
* (2) facilitative GLUT transportercite journal |author=Uldry M, Thorens B|title=The SLC2 family of facilitated hexose and polyol transporters|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 480–489 |year= 2004|doi= 10.1007/s00424-003-1085-0 |pmid= 12750891]
** (SLC2A1, SLC2A2, SLC2A3, SLC2A4, SLC2A5, SLC2A6, SLC2A7, SLC2A8, SLC2A9, SLC2A10, SLC2A11, SLC2A12, SLC2A13, SLC2A14)
* (3) heavy subunits of heteromeric amino acid transporterscite journal |author=Palacin M, Kanai Y|title=The ancillary proteins of HATs: SLC3 family of amino acid transporters|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 490–494 |year= 2004|doi= 10.1007/s00424-003-1062-7 |pmid= 14770309]
** (SLC3A1, SLC3A2)
* (4) bicarbonate transportercite journal |author=Romero MF, Fulton CM, Boron WF|title=The SLC4 family of HCO 3 - transporters|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 490–494 |year= 2004|doi= 10.1007/s00424-003-1180-2 |pmid= 14722772]
** (SLC4A1, SLC4A1, SLC4A2, SLC4A3, SLC4A4, SLC4A5, SLC4A6, SLC4A7, SLC4A8, SLC4A9, SLC4A10, SLC4A11)
* (5) sodium glucose cotransportercite journal |author=Wright EM, Turk E|title=The sodium/glucose cotransport family SLC5|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 510–518 |year= 2004|doi= 10.1007/s00424-003-1063-6 |pmid= 14722772]
** (SLC5A1, SLC5A2, SLC5A3, SLC5A4, SLC5A5, SLC5A6, SLC5A7, SLC5A8, SLC5A9, SLC5A10, SLC5A11, SLC5A12)
* (6) sodium- and chloride- dependent cite journal |author=Chen NH, Reith ME, Quick MW|title=Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6|journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 519–531 |year= 2004|doi= 10.1007/s00424-003-1064-5 |pmid= 12719981]
** (SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC6A10, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A20)
* (7) cationic amino acid transporter/glycoprotein-associatedcite journal |author=Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y |title=CATs and HATs: the SLC7 family of amino acid transporters |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 532–542 |year= 2004 |doi = 10.1007/s00424-003-1086-z |pmid= 14770310]
** (SLC7A1, SLC7A2, SLC7A3, SLC7A4, SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC7A14)
* (8) Na+/Ca2+ exchangercite journal |author=Quednau BD, Nicoll DA, Philipson KD |title=The sodium/calcium exchanger family-SLC8 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 543–548 |year= 2004 |doi = 10.1007/s00424-003-1065-4 |pmid= 12734757]
** (SLC8A1, SLC8A2, SLC8A3)
* (9) Na+/H+ exchangercite journal |author=Orlowski J, Grinstein S |title=Diversity of the mammalian sodium/proton exchanger SLC9 gene family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 549–565 |year= 2004 |doi = 10.1007/s00424-003-1110-3 |pmid= 12845533]
** (SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11)
* (10) sodium bile salt cotransportcite journal |author=Hagenbuch B, Dawson P |title=The sodium bile salt cotransport family SLC10 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 566–570 |year= 2004 |doi = 10.1007/s00424-003-1130-z |pmid= 12851823]
** (SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC10A6, SLC10A7)
* (11) proton coupled metal ioncite journal |author=Mackenzie B, Hediger MA |title=SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 571–579 |year= 2004 |doi = 10.1007/s00424-003-1141-9 |pmid= 14530973]
** transporter (SLC11A1, SLC11A2)
* (12) electroneutral cation-Cl cotransportercite journal |author=Hebert SC, Mount DB, Gamba G |title=Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 580–593 |year= 2004 |doi = 10.1007/s00424-003-1066-3 |pmid= 12739168]
** (SLC12A1, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9)
* (13) human Na+-sulfate/carboxylate cotransportercite journal |author=Markovich D, Murer H |title=The SLC13 gene family of sodium sulphate/carboxylate cotransporters |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 594–602 |year= 2004 |doi = 10.1007/s00424-003-1207-8 |pmid= 12915942]
** (SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5)
* (14) urea transportercite journal |author=Shayakul C, Hediger MA |title=The SLC14 gene family of urea transporters |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 603–609 |year= 2004 |doi = 10.1007/s00424-003-1124-x |pmid= 12856182]
** (SLC14A1, SLC14A2)
* (15) proton oligopeptide cotransportercite journal |author=Daniel H, Kottra G |title=The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 610–618 |year= 2004 |doi = 10.1007/s00424-003-1101-4 |pmid= 12905028]
** (SLC15A1, SLC15A2, SLC15A3, SLC15A4)
* (16) monocarboxylate transportercite journal |author=Halestrap AP, Meredith D |title=The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 619–628 |year= 2004 |doi = 10.1007/s00424-003-1067-2 |pmid= 12739169]
** (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14)
* (17) vesicular glutamate transportercite journal |author=Reimer RJ, Edwards RH |title=Organic anion transport is the primary function of the SLC17/type I phosphate transporter family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 629–635 |year= 2004 |doi = 10.1007/s00424-003-1087-y |pmid= 12811560]
** (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8)
* (18) vesicular amine transportercite journal |author=Eiden LE, Schafer MK, Weihe E, Schutz B |title=The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 636–640 |year= 2004 |doi = 10.1007/s00424-003-1100-5 |pmid= 12827358]
** (SLC18A1, SLC18A2, SLC18A3)
* (19) folate/thiamine transportercite journal |author=Ganapathy V, Smith SB, Prasad PD |title=SLC19: the folate/thiamine transporter family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 641–646 |year= 2004 |doi = 10.1007/s00424-003-1068-1 |pmid= 14770311]
** (SLC19A1, SLC19A2, SLC19A3)
* (20) type III Na+-phosphate cotransportercite journal |author=Collins JF, Bai L, Ghishan FK |title=The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 641–646 |year= 2004 |doi = 10.1007/s00424-003-1088-x |pmid= 12759754 ]
** (SLC20A1, SLC20A2)
* (21) organic anion transportingcite journal |author=Hagenbuch B, Meier PJ |title=Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 653–665 |year= 2004 |doi = 10.1007/s00424-003-1168-y |pmid= 14579113 ]
** subfamily 1 (SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B4, SLCO1C1)
** subfamily 2 (SLCO2A1, SLCO2B1)
** subfamily 3 (SLCO3A1)
** subfamily 4 (SLCO4A1, SLCO4C1)
** subfamily 5 (SLCO5A1)
** subfamily 6 (SLCO6A1)
* (22) organic cation/anion/zwitterion transportercite journal |author=Koepsell H, Endou H |title=The SLC22 drug transporter family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 666–676 |year= 2004 |doi = 10.1007/s00424-003-1089-9 |pmid= 12883891]
** (SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A10, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A19, SLC22A20)
* (23) Na+-dependent ascorbic acid transportercite journal |author=Takanaga H, Mackenzie B, Hediger MA |title=Sodium-dependent ascorbic acid transporter family SLC23 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 677–682 |year= 2004 |doi = 10.1007/s00424-003-1104-1 |pmid= 12845532]
** (SLC23A1, SLC23A2, SLC23A3, SLC23A4)
* (24) Na+/(Ca2+-K+) exchangercite journal |author=Schnetkamp PP |title=The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 683–688 |year= 2004 |doi = 10.1007/s00424-003-1069-0 |pmid= 14770312]
** (SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6)
* (25) mitochondrial carriercite journal |author=Palmieri F |title=The mitochondrial transporter family (SLC25): physiological and pathological implications |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 689–709 |year= 2004 |doi = 10.1007/s00424-003-1099-7 |pmid= 14598172]
** (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, 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)
* (26) multifunctional anion exchangercite journal |author=Mount DB, Romero MF |title=The SLC26 gene family of multifunctional anion exchangers |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 710–721 |year= 2004 |doi = 10.1007/s00424-003-1090-3 |pmid= 12759755]
** (SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11)
* (27) fatty acid transport proteincite journal |author=Stahl A |title=A current review of fatty acid transport proteins (SLC27) |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 722–727 |year= 2004 |doi = 10.1007/s00424-003-1106-z |pmid= 12856180]
** (SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, SLC27A6)
* (28) Na+-coupled nucleoside transportcite journal |author=Gray JH, Owen RP, Giacomini KM |title=The concentrative nucleoside transporter family, SLC28 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 728–734 |year= 2004 |doi = 10.1007/s00424-003-1107-y |pmid= 12856181]
** (SLC28A1, SLC28A2, SLC28A3)
* (29) facilitative nucleoside transportercite journal |author=Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD |title=The equilibrative nucleoside transporter family, SLC29 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 735–743 |year= 2004 |doi = 10.1007/s00424-003-1103-2 |pmid= 12838422]
** (SLC29A1, SLC29A2, SLC29A3, SLC29A4)
* (30) zinc effluxcite journal |author=Palmiter RD, Huang L |title=Efflux and compartmentalization of zinc by members of the SLC30 family ofsolute carriers |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 744–751 |year= 2004 |doi = 10.1007/s00424-003-1070-7 |pmid= 12748859]
** (SLC30A1, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A8, SLC30A9, SLC30A10)
* (31) copper transportercite journal |author=Petris MJ |title=The SLC31 (Ctr) copper transporter family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 752–755 |year= 2004 |doi = 10.1007/s00424-003-1092-1 |pmid= 12827356]
** (SLC31A1)
* (32) vesicular inhibitory amino acid transportercite journal |author=Gasnier B |title=The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 752–755 |year= 2004 |doi = 10.1007/s00424-003-1091-2 |pmid= 12750892]
** (SLC32A1)
* (33) Acety-CoA transportercite journal |author=Hirabayashi Y, Kanamori A, Nomura KH, Nomura K |title=The acetyl-CoA transporter family SLC33 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 760–762 |year= 2004 |doi = 10.1007/s00424-003-1071-6 |pmid= 12739170]
** (SLC33A1)
* (34) type II Na+-phosphate cotransportercite journal |author=Murer H, Forster I, Biber J |title=The sodium phosphate cotransporter family SLC34 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 763–767 |year= 2004 |doi = 10.1007/s00424-003-1072-5 |pmid= 12750889]
** (SLC34A1, SLC34A2, SLC34A3)
* (35) nucleoside-sugar transportercite journal |author=Ishida N, Kawakita M |title=Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35) |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 768–775 |year= 2004 |doi = 10.1007/s00424-003-1093-0 |pmid= 12759756]
** 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, SLC35E2, SLC35E3, SLC35E4)
* (36) proton-coupled amino acid transportercite journal |author=Boll M, Daniel H, Gasnier B |title=The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 776–779 |year= 2004 |doi = 10.1007/s00424-003-1073-4 |pmid= 12748860]
** (SLC36A1, SLC36A2, SLC36A3, SLC36A4)
* (37) sugar-phosphate/phosphate exchangercite journal |author=Bartoloni L, Antonarakis SE |title=The human sugar-phosphate/phosphate exchanger family SLC37 |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 780–783 |year= 2004 |doi = 10.1007/s00424-003-1105-0 |pmid= 12811562]
** (SLC37A1, SLC37A2, SLC37A3, SLC37A4)
* (38) System A & N, sodium-coupled neutral amino acid transportercite journal |author=Mackenzie B, Erickson JD |title=Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 784–795 |year= 2004 |doi = 10.1007/s00424-003-1117-9 |pmid= 12845534]
** (SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6)
* (39) metal ion transportercite journal |author=Eide DJ |title=The SLC39 family of metal ion transporters |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 796–800 |year= 2004 |doi = 10.1007/s00424-003-1074-3 |pmid= 12748861]
** (SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14)
* (40) basolateral iron transportercite journal |author=McKie AT, Barlow DJ |title=The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1) |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 801–806 |year= 2004 |doi = 10.1007/s00424-003-1102-3 |pmid= 12836025]
** (SLC40A1)
* (41) MgtE-like magnesium transporter
** (SLC41A1, SLC41A2, SLC41A3)
* (42) Rh ammonium transportercite journal |author=Nakhoul NL, Hamm LL |title=Non-erythroid Rh glycoproteins: a putative new family of mammalian ammonium transporters |journal= Pflugers Arch |volume= 447 |issue= 5 |pages= 807–812 |year= 2004 |doi = 10.1007/s00424-003-1142-8 |pmid= 12920597]
** (RHAG, RhBG, RhCG)
* (43) Na+-independent, system-L like amino acid transporter
** (SLC43A1, SLC43A2, SLC43A3)
* (44) Choline-like transporter
** (SLC44A1, SLC44A2, SLC44A3, SLC44A4, SLC44A5)
* (45) Putative sugar transporter
** (SLC45A1, SLC45A2, SLC54A3, SLC45A4)
* (46) Heme transporter
** (SLC46A1, SLC46A2)
* (47) multidrug and toxin extrusion
** (SLC47A1, SLC47A2)

References

External links

* [http://www.bioparadigms.org/slc/menu.asp Outline of families]
* [http://www.gene.ucl.ac.uk/nomenclature/genefamily/slc.php List of proteins at gene.ucl.ac.uk]