SLC66A3
| SLC66A3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SLC66A3, C2orf22, PQ loop repeat containing 3, solute carrier family 66 member 3, PQLC3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 2444067; HomoloGene: 16454; GeneCards: SLC66A3; OMA:SLC66A3 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
Gene
[edit]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]
Transcripts
[edit]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
[edit]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]
Secondary structure
[edit]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
[edit]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
[edit]Promoter
[edit]The promoter of SLC66A3 is 1,169 base pairs long and is located 1000 base pairs upstream of the 5' UTR.
Transcription factors
[edit]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
[edit]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
[edit]Post translational modifications
[edit]SLC66A3 is predicted to undergo phosphorylation, N-glycosylation, and myristoylation.[17][18]
Homology/Evolution
[edit]
Orthologs
[edit]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
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000162976 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045679 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ a b c "SLC66A3 Gene". www.genecards.org. Retrieved 2021-10-06.
- ^ 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) - ^ "SAPS Results". www.ebi.ac.uk. Retrieved 2021-12-21.
- ^ "I-TASSER results". zhanggroup.org. Retrieved 2021-12-21.
- ^ "DiANNA". bioinformatics.bc.edu. Retrieved 2021-12-21.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "Motif Scan". myhits.sib.swiss. Retrieved 2021-12-21.
- ^ "Services". www.healthtech.dtu.dk. Retrieved 2021-12-21.