SLC66A3

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
Orthologs
SpeciesHumanMouse
Entrez

130814

217430

Ensembl

ENSG00000162976

ENSMUSG00000045679

UniProt

Q8N755

Q8C6U2

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

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

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

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

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

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

Promoter

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

Transcription factors

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

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

Post translational modifications

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

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

Orthologs

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
  1. GRCh38: Ensembl release 89: ENSG00000162976 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000045679 - Ensembl, 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. "SLC66A3 solute carrier family 66 member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-19.
  7. "SLC66A3 Gene". www.genecards.org. Retrieved 2021-10-06.
  8. "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. "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.
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