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.
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:
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
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.
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.
^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.
PMID14624363.
S2CID1866661.
^
abPerland 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.
PMID27939446.
^Daniel H, Kottra G (February 2004). "The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology". Pflügers Archiv. 447 (5): 610–618.
doi:
10.1007/s00424-003-1101-4.
PMID12905028.
S2CID22369521.
^Halestrap AP, Meredith D (February 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv. 447 (5): 619–628.
doi:
10.1007/s00424-003-1067-2.
PMID12739169.
S2CID15498611.
^Reimer RJ, Edwards RH (February 2004). "Organic anion transport is the primary function of the SLC17/type I phosphate transporter family". Pflügers Archiv. 447 (5): 629–635.
doi:
10.1007/s00424-003-1087-y.
PMID12811560.
S2CID9680597.
^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.
PMID12827358.
S2CID20764857.
^Collins JF, Bai L, Ghishan FK (February 2004). "The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors". Pflügers Archiv. 447 (5): 647–652.
doi:
10.1007/s00424-003-1088-x.
PMID12759754.
S2CID7737512.
^Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (February 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–743.
doi:
10.1007/s00424-003-1103-2.
PMID12838422.
S2CID8817821.
^Palmiter RD, Huang L (February 2004). "Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers". Pflügers Archiv. 447 (5): 744–751.
doi:
10.1007/s00424-003-1070-7.
PMID12748859.
S2CID725350.
^Ishida N, Kawakita M (February 2004). "Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)". Pflügers Archiv. 447 (5): 768–775.
doi:
10.1007/s00424-003-1093-0.
PMID12759756.
S2CID8690030.
^Boll M, Daniel H, Gasnier B (February 2004). "The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis". Pflügers Archiv. 447 (5): 776–779.
doi:
10.1007/s00424-003-1073-4.
PMID12748860.
S2CID25655241.
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.
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:
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
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.
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.
^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.
PMID14624363.
S2CID1866661.
^
abPerland 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.
PMID27939446.
^Daniel H, Kottra G (February 2004). "The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology". Pflügers Archiv. 447 (5): 610–618.
doi:
10.1007/s00424-003-1101-4.
PMID12905028.
S2CID22369521.
^Halestrap AP, Meredith D (February 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv. 447 (5): 619–628.
doi:
10.1007/s00424-003-1067-2.
PMID12739169.
S2CID15498611.
^Reimer RJ, Edwards RH (February 2004). "Organic anion transport is the primary function of the SLC17/type I phosphate transporter family". Pflügers Archiv. 447 (5): 629–635.
doi:
10.1007/s00424-003-1087-y.
PMID12811560.
S2CID9680597.
^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.
PMID12827358.
S2CID20764857.
^Collins JF, Bai L, Ghishan FK (February 2004). "The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors". Pflügers Archiv. 447 (5): 647–652.
doi:
10.1007/s00424-003-1088-x.
PMID12759754.
S2CID7737512.
^Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (February 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–743.
doi:
10.1007/s00424-003-1103-2.
PMID12838422.
S2CID8817821.
^Palmiter RD, Huang L (February 2004). "Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers". Pflügers Archiv. 447 (5): 744–751.
doi:
10.1007/s00424-003-1070-7.
PMID12748859.
S2CID725350.
^Ishida N, Kawakita M (February 2004). "Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)". Pflügers Archiv. 447 (5): 768–775.
doi:
10.1007/s00424-003-1093-0.
PMID12759756.
S2CID8690030.
^Boll M, Daniel H, Gasnier B (February 2004). "The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis". Pflügers Archiv. 447 (5): 776–779.
doi:
10.1007/s00424-003-1073-4.
PMID12748860.
S2CID25655241.