Solute carrier family 66 member 3 is a gene in humans that encodes the protein SLC66A3. The function of the SLC66A3 protein is not yet well understood but belongs to a family of five evolutionarily related proteins, the SLC66 lysosomal amino acid transporters.[5] SLC66A3 is localized to the endoplasmic reticulum and has four transmembrane domains.[6]

SLC66A3
Identifiers
AliasesSLC66A3, C2orf22, PQ loop repeat containing 3, solute carrier family 66 member 3, PQLC3
External IDsMGI: 2444067; HomoloGene: 16454; GeneCards: SLC66A3; OMA:SLC66A3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001282710
NM_001282711
NM_001282712
NM_152391

NM_001161111
NM_172574

RefSeq (protein)

NP_001269639
NP_001269640
NP_001269641
NP_689604

NP_766162

Location (UCSC)Chr 2: 11.16 – 11.18 MbChr 12: 17.04 – 17.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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The SLC66A3 is a gene consisting of 26,831 base pairs spanning from 11,155,467 to 11,178,856 on chromosome 2.[6] SLC66A3 mapped to the plus strand at 2p25.1 and contains 7 exons.[7] The SLC66A3 gene is neighbored by the genes ROCK2, C2orf50, and KCNF1.[6] ROCK2 and C2orf50 are both located upstream of SLC66A3 whereas KCNF1 is located upstream.[6]

 
Chromosome 2. SLC66A3 is located at 2p25.1

Transcripts

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SLC66A3 has 14 different mRNAs, there are 12 alternatively-spliced mRNAs that produce functional proteins and 2 unspliced variations that do not.[6] The longest transcript is transcript variant 1 which produces the longest protein at 202 amino acids in length.

Protein

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The SLC66A3 protein coding gene that produces a protein with the same name.[8] The mRNA transcript variant 1 is 1,717 bp with 7 exons and produces the longest protein, transcript variant 1. SLC66A3 is a 202 amino acid, 22.6 kDa protein with a theoretical isoelectric point of 9.14.[9]

 
Conceptual Translation of SLC66A3

Secondary structure

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The secondary structure of SLC66A3 is predicted to consist of 7 α-helices. The protein contains a signal peptide, 4 transmembrane regions, and a splicing variant region, and is localized in the endoplasmic reticulum.[7][8]

Tertiary structure

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I-TASSER predicts that the tertiary structure contains 7 coils with high certainty.[10] DiANNA predicts disulfide bonds between positions 9 - 57, 17 - 121, and 82 - 157.[11]

Gene level regulation

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Promoter

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The promoter of SLC66A3 is 1,169 base pairs long and is located 1000 base pairs upstream of the 5' UTR.

Transcription factors

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Many different transcription factors regulate the expression of the SLC66A3 gene. Some of these include RNA polymerase II transcription factor II B, Myc associated zinc fingers, EGR/nerve growth factor induced protein C & related factors, and EVI1-myeloid transforming protein.

Transcription Factor Function
RNA polymerase II transcription factor II B Stimulation of transcription initiation.[12]
EVI1-myleoid transforming protein Involved in the proliferation and differentiation of hematopoietic cells through interaction with GATA-2.[13]
Krueppel like transcription factors Involved in β-globin expression and the development of erythrocytes.[14]
GATA binding factors Involved in the regulation of transcription during developmental stages and maintaining and developing hematopoietic systems.[15]

Expression patterns

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SLC66A3 is expressed at high levels in a variety of tissues throughout the body but is most highly abundant in the whole blood and white blood cells.[6][16] SLC66A3 is expressed at high levels, approximately 2.1 times more than the average gene.[16]

Protein Level Regulation

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Post translational modifications

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SLC66A3 is predicted to undergo phosphorylation, N-glycosylation, and myristoylation.[17][18]

Homology/Evolution

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Date of divergence vs corrected divergence of SLC66A3 orthologs compared to cytochrome c and fibrinogen alpha.

Orthologs

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SLC66A3 was present in the common ancestor of animals and is found in all animals but not fungi.[7]

Genus, Species Common Name Taxonomic Group Divergence date from humans (MYA) accession number Sequence Length(AA) Sequence Identity(%)
Homo sapiens Human Primates 0 NP_689604.1 202 100
Mus musculus Mouse Rodentia 89 NP_766162.2 202 85
Phascolarctos cinereus Koala Marsupialia 160 XP_020841056.1 203 74
Anolis carolinensis Green anole Squamata 318 XP_003215467.1 202 64
Gallus gallus Chicken Galliformes 318 XP_040524789.1 201 71
Danio rerio Zebrafish Cypriniformes 433 NP_001004615.1 203 59
Electrophorus electricus Electric eel Gymnotiformes 433 XP_026863988.2 203 58
Callorhinchus milii Elephant shark Chimaera 465 XP_007895274.1 218 59
Petromyzon marinus Sea lamprey Petromyzontiformes 599 XP_032825995.1 201 52
Crassostrea gigas Pacific oyster Ostreida 736 XP_034312411.1 208 36
Drosophila willistoni Fruitfly Diptera 736 XP_002074377.2 220 34
Owenia fusiformis Tube worm Canalipalpata 736 CAC9661908.1 233 29
Lytechinus variegatus Variegated sea urchin Temnopleuroida 627 XP_041484893.1 224 29
Asterias rubens Common starfish Forcipulatida 627 XP_033644897.1 213 28
Amphimedon queenslandica Sponge Haplosclerida 777 XP_019856231.1 221 26

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162976Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045679Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Gyimesi G, Hediger MA (2021-06-25). "SLC66 Lysosomal amino acid transporters in GtoPdb v.2021.2". IUPHAR/BPS Guide to Pharmacology CITE. 2021 (2). doi:10.2218/gtopdb/F1048/2021.2. ISSN 2633-1020. S2CID 237877056.
  6. ^ a b c d e f "SLC66A3 solute carrier family 66 member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-19.
  7. ^ a b c "SLC66A3 Gene". www.genecards.org. Retrieved 2021-10-06.
  8. ^ a b "Homo sapiens solute carrier family 66 member 3 (SLC66A3), transcript variant 1, mRNA". 2021-02-16. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ "SAPS Results". www.ebi.ac.uk. Retrieved 2021-12-21.
  10. ^ "I-TASSER results". zhanggroup.org. Retrieved 2021-12-21.
  11. ^ "DiANNA". bioinformatics.bc.edu. Retrieved 2021-12-21.
  12. ^ Liu X, Bushnell DA, Kornberg RD (January 2013). "RNA polymerase II transcription: structure and mechanism". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1829 (1): 2–8. doi:10.1016/j.bbagrm.2012.09.003. PMC 4244541. PMID 23000482.
  13. ^ Yuan X, Wang X, Bi K, Jiang G (December 2015). "The role of EVI-1 in normal hematopoiesis and myeloid malignancies (Review)". International Journal of Oncology. 47 (6): 2028–2036. doi:10.3892/ijo.2015.3207. PMID 26496831.
  14. ^ Pollak NM, Hoffman M, Goldberg IJ, Drosatos K (February 2018). "Krüppel-like factors: Crippling and un-crippling metabolic pathways". JACC. Basic to Translational Science. 3 (1): 132–156. doi:10.1016/j.jacbts.2017.09.001. PMC 5985828. PMID 29876529.
  15. ^ Gao J, Chen YH, Peterson LC (2015-10-06). "GATA family transcriptional factors: emerging suspects in hematologic disorders". Experimental Hematology & Oncology. 4 (1): 28. doi:10.1186/s40164-015-0024-z. PMC 4594744. PMID 26445707.
  16. ^ a b "AceView: Gene:PQLC3, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2021-12-19.
  17. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2021-12-21.
  18. ^ "Services". www.healthtech.dtu.dk. Retrieved 2021-12-21.