Amino Acids - Part 1- Intolerance
This blog post is one of several that will be forthcoming related to amino acids. This article is focused on a particular family of amino acid transporters, SLC7A1-14, which is involved in the transport of many different amino acids (depending on the particular gene - see below). If you believe you have had intolerance to supplementing with specific amino acids - it may be worthwhile checking into the status of the particular relevant gene(s) noted below. In the interim, i have kept the material here simple, and from one source from now - Gene Cards. It is very basic, but should allow you to take the first steps in checking out if this family of transporters may be causing amino acid intolerance. Some aminos covered by this family of transporters are: Lysine, Arginine, Tyrosine, Phenylalinine, Trypotophan, Histadine, Ornithine, Cysteine, Glutamine, etc.
Amino Acids SLC7A Transporters
SLC7A1 Lys, Arg, Orn System y+
Entrez Gene Summary
Enables L-arginine transmembrane transporter activity and L-histidine transmembrane transporter activity. Involved in amino acid transport. Located in membrane. Part of apical plasma membrane; basolateral plasma membrane; and protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary
SLC7A1 (Solute Carrier Family 7 Member 1) is a Protein Coding gene. Diseases associated with SLC7A1 include Aids Phobia and Tinea Capitis. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Nanog in Mammalian ESC Pluripotency. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and L-ornithine transmembrane transporter activity. An important paralog of this gene is SLC7A2.
UniProtKB/Swiss-Prot Summary
High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues. ( CTR1_HUMAN,P30825 )
SLC7A2 Lys, Arg, Orn System y+ SLC7A2-related argininemia
Entrez Gene Summary
The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
GeneCards Summary
SLC7A2 (Solute Carrier Family 7 Member 2) is a Protein Coding gene. Diseases associated with SLC7A2 include Asthma. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and basic amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A1.
UniProtKB/Swiss-Prot Summary
Functions as permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine); the affinity for its substrates differs between isoforms created by alternative splicing (PubMed:9174363). May play a role in classical or alternative activation of macrophages via its role in arginine transport (By similarity). ( CTR2_HUMAN,P52569 )
[Isoform 1]: Functions as permease that mediates the transport of the cationic amino acids (arginine, lysine and ornithine), and it has much higher affinity for arginine than isoform 2. ( CTR2_HUMAN,P52569 )
[Isoform 2]: Functions as low-affinity, high capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine). ( CTR2_HUMAN,P52569 )
SLC7A3 Lys, Arg, Orn System y+
Entrez Gene Summary
This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]
GeneCards Summary
SLC7A3 (Solute Carrier Family 7 Member 3) is a Protein Coding gene. Diseases associated with SLC7A3 include Congenital Aphakia and Alcoholic Ketoacidosis. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and basic amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A1.
UniProtKB/Swiss-Prot Summary
Mediates the uptake of the cationic amino acids arginine, lysine and ornithine in a sodium-independent manner. ( CTR3_HUMAN,Q8WY07 )
SLC7A4 Cationic AA System y+
Entrez Gene Summary
Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary
SLC7A4 (Solute Carrier Family 7 Member 4) is a Protein Coding gene. Diseases associated with SLC7A4 include Velocardiofacial Syndrome and Rubeosis Iridis. Among its related pathways are 22q11.2 copy number variation syndrome. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and basic amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A3.
UniProtKB/Swiss-Prot Summary
Involved in the transport of the cationic amino acids (arginine, lysine and ornithine). ( CTR4_HUMAN,O43246 )
SLC7A5 Leu, Hys, Met, Ile, Val, Phe, Tyr, Trp System
Entrez Gene Summary
Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary
SLC7A5 (Solute Carrier Family 7 Member 5) is a Protein Coding gene. Diseases associated with SLC7A5 include Lysinuric Protein Intolerance and Phenylketonuria. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Blood-Brain Barrier and Immune Cell Transmigration: Overview. Gene Ontology (GO) annotations related to this gene include peptide antigen binding and antiporter activity. An important paralog of this gene is SLC7A8.
UniProtKB/Swiss-Prot Summary
The heterodimer with SLC3A2 functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine, methionine and tryptophan (PubMed:9751058, 10049700, 11557028, 10391915, 10574970, 11311135, 11564694, 12117417, 12225859, 25998567, 30867591). Functions as an amino acid exchanger (PubMed:11557028, 12117417, 12225859, 30867591). May play a role in the transport of L-DOPA across the blood-brain barrier (By similarity). May act as the major transporter of tyrosine in fibroblasts (Probable). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity). Can mediate the transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694, 12225859). When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane (PubMed:15769744). ( LAT1_HUMAN,Q01650 )
(Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. ( LAT1_HUMAN,Q01650 )
SLC7A6 Lys, Arg, Orn, Hys, Met, Leu System y+
Entrez Gene Summary
Enables basic amino acid transmembrane transporter activity. Involved in basic amino acid transmembrane transport and ornithine transport. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary
SLC7A6 (Solute Carrier Family 7 Member 6) is a Protein Coding gene. Diseases associated with SLC7A6 include Lysinuric Protein Intolerance and Hepatocellular Carcinoma. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and L-amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A7.
UniProtKB/Swiss-Prot Summary
Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires coexpression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine and glutamine. Also acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Involved in the transport of L-arginine in monocytes. Reduces uptake of ornithine in retinal pigment epithelial (RPE) cells. ( YLAT2_HUMAN,Q92536 )
SLC7A7 Lys, Arg, Orn, Hys, Met, Leu, Ala, Cys System y+L Lysinuric protein intolerance
Entrez Gene Summary
The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]
GeneCards Summary
SLC7A7 (Solute Carrier Family 7 Member 7) is a Protein Coding gene. Diseases associated with SLC7A7 include Lysinuric Protein Intolerance and Autoinflammatory Syndrome. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Disorders of transmembrane transporters. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and L-amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A6.
UniProtKB/Swiss-Prot Summary
Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires coexpression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine and glutamine. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Involved in the transport of L-arginine in monocytes. ( YLAT1_HUMAN,Q9UM01 )
SLC7A8 Neutral AA System L
Entrez Gene Summary for SLC7A8 Gene
Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral plasma membrane and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary for SLC7A8 Gene
SLC7A8 (Solute Carrier Family 7 Member 8) is a Protein Coding gene. Diseases associated with SLC7A8 include Lysinuric Protein Intolerance and Cystinuria. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include peptide antigen binding and antiporter activity. An important paralog of this gene is SLC7A10.
UniProtKB/Swiss-Prot Summary for SLC7A8 Gene
Sodium-independent, high-affinity transport of small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. ( LAT2_HUMAN,Q9UHI5 )
SLC7A9 Cys, dibasic and neutral AA System b0,+ Cystinuria
Entrez Gene Summary for SLC7A9 Gene
This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]
GeneCards Summary for SLC7A9 Gene
SLC7A9 (Solute Carrier Family 7 Member 9) is a Protein Coding gene. Diseases associated with SLC7A9 include Cystinuria and Ureteral Disease. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Disorders of transmembrane transporters. Gene Ontology (GO) annotations related to this gene include peptide antigen binding and antiporter activity. An important paralog of this gene is SLC7A5.
UniProtKB/Swiss-Prot Summary for SLC7A9 Gene
Involved in the high-affinity, sodium-independent transport of cystine and neutral and dibasic amino acids (system b(0,+)-like activity). Thought to be responsible for the high-affinity reabsorption of cystine in the kidney tubule. ( BAT1_HUMAN,P82251 )
SLC7A10 Gly, Ala, Ser, Cys, Thr System ASC
Entrez Gene Summary for SLC7A10 Gene
SLC7A10, in association with 4F2HC (SLC3A2; MIM 158070), mediates high-affinity transport of D-serine and several other neutral amino acids (Nakauchi et al., 2000 [PubMed 10863037]).[supplied by OMIM, Mar 2008]
GeneCards Summary for SLC7A10 Gene
SLC7A10 (Solute Carrier Family 7 Member 10) is a Protein Coding gene. Diseases associated with SLC7A10 include Cystinuria and Hyperekplexia. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and neutral L-amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A8.
UniProtKB/Swiss-Prot Summary for SLC7A10 Gene
Sodium-independent, high affinity transport of small neutral D- and L-amino acids. May play a role in the modulation of glutamatergic transmission through mobilization of D-serine at the glutamatergic synapse. ( AAA1_HUMAN,Q9NS82 )
SLC7A11 Glu, Asp, Cys System y+
Entrez Gene Summary for SLC7A11 Gene
This gene encodes a member of a heteromeric, sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate. In this system, designated Xc(-), the anionic form of cysteine is transported in exchange for glutamate. This protein has been identified as the predominant mediator of Kaposi sarcoma-associated herpesvirus fusion and entry permissiveness into cells. Also, increased expression of this gene in primary gliomas (compared to normal brain tissue) was associated with increased glutamate secretion via the XCT channels, resulting in neuronal cell death. [provided by RefSeq, Sep 2011]
GeneCards Summary for SLC7A11 Gene
SLC7A11 (Solute Carrier Family 7 Member 11) is a Protein Coding gene. Diseases associated with SLC7A11 include Lysinuric Protein Intolerance and Cystinuria. Among its related pathways are Nuclear events mediated by NFE2L2 and Transport of inorganic cations/anions and amino acids/oligopeptides. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and cystine:glutamate antiporter activity. An important paralog of this gene is SLC7A5.
UniProtKB/Swiss-Prot Summary for SLC7A11 Gene
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate. ( XCT_HUMAN,Q9UPY5 )
SLC7A12 Gly, Ala, Ser, Cys, Thr System
Enables amino acid transmembrane transporter activity. Acts upstream of or within amino acid transport. Located in cytoplasm and plasma membrane. Orthologous to human SLC7A13 (solute carrier family 7 member 13). [provided by Alliance of Genome Resources, Apr 2022]
SLC7A13 Glu, Asp, Cys Glu/Asp/Cys transporter Cystinuria
Entrez Gene Summary for SLC7A13 Gene
Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in L-cystine transport; L-glutamate transmembrane transport; and aspartate transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
GeneCards Summary for SLC7A13 Gene
SLC7A13 (Solute Carrier Family 7 Member 13) is a Protein Coding gene.
Diseases associated with SLC7A13 include Developmental And Epileptic Encephalopathy 3 and Retinitis Pigmentosa 68. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and L-amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A6.
UniProtKB/Swiss-Prot Summary for SLC7A13 Gene
Mediates the transport L-aspartate and L-glutamate in a sodium-independent manner. ( S7A13_HUMAN,Q8TCU3 )
SLC7A14 Arg, Lys, Orn System C Retinitis pigmentosa 68
Entrez Gene Summary
This gene is predicted to encode a glycosylated, cationic amino acid transporter protein with 14 transmembrane domains. This gene is primarily expressed in skin fibroblasts, neural tissue, and primary endothelial cells and its protein is predicted to mediate lysosomal uptake of cationic amino acids. Mutations in this gene are associated with autosomal recessive retinitis pigmentosa. In mice, this gene is expressed in the photoreceptor layer of the retina where its expression increases over the course of retinal development and persists in the mature retina. [provided by RefSeq, Apr 2014]
GeneCards Summary
SLC7A14 (Solute Carrier Family 7 Member 14) is a Protein Coding gene. Diseases associated with SLC7A14 include Retinitis Pigmentosa 68 and Retinitis Pigmentosa. Gene Ontology (GO) annotations related to this gene include amino acid transmembrane transporter activity and L-amino acid transmembrane transporter activity. An important paralog of this gene is SLC7A1.
[1] Gene Cards Summary from www.genecards.org
[2] Entrez summary from www.genecards.org
[3] UniProtKB/Swiss-Prot Summaries from www.genecards.org